scholarly journals A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime, and K048) in vivo detected by biochemical and histochemical techniques

2010 ◽  
Vol 25 (6) ◽  
pp. 790-797 ◽  
Author(s):  
Jiri Bajgar ◽  
Petr Hajek ◽  
Jana Karasova Zdarova ◽  
Jiri Kassa ◽  
Antonin Paseka ◽  
...  
Keyword(s):  
Rat Brain ◽  
Hi 6 ◽  
Acetylcholinesterase Reactivation ◽  
Brain Acetylcholinesterase

Oximes-induced reactivation of rat brain acetylcholinesterase inhibited by VX agent

2004 ◽  
Vol 23 (4) ◽  
pp. 167-171 ◽  
Author(s):  
Kamil Kuča ◽  
Jiří Kassa
Keyword(s):  
Rat Brain ◽  
Brain Homogenate ◽  
Hi 6 ◽  
Brain Acetylcholinesterase

A comparison of one mono- and seven bisquaternary acetylcholinesterase (AChE) reactivators of acetylcholinesterase inhibited by VX agent was performed. As a source of the acetylcholinesterase, a rat brain homogenate was taken. There were significant differences in reactivation potency of all tested oximes. The oxime TO205 seems to be the most efficacious followed by TO046, HI-6, HS-6, K027, obidoxime, MMC and 2-PAM. In addition, the results of this study showed that the reactivation potency of the tested reactivators depends on many factors-such as the number of pyridinium rings, the number of oxime groups and their position, as well as the length and the shape of linkage bridge between two pyridinium rings.

The Reactivating and Therapeutic Efficacy of Oximes to Counteract Russian VX Poisonings

2006 ◽  
Vol 25 (5) ◽  
pp. 397-401 ◽  
Author(s):  
Jiri Kassa ◽  
Daniel Jun ◽  
Kamil Kuca
Keyword(s):  
Therapeutic Efficacy ◽  
Central Compartment ◽  
Toxic Effects ◽  
Peripheral Compartment ◽  
Structural Analogue ◽  
Hi 6 ◽  
Alkyl Groups ◽  
Brain Acetylcholinesterase ◽  
Acute Toxic

Russian VX ( O-isobutyl- S-(2-diethylaminoethyl)methylphosphonothioate) is the structural analogue of VX agent. It differs from VX agent ( O-ethyl- S-(2-diisopropylaminoethyl) methylphosphonothioate) by two alkyl groups. The potency of currently available oximes (pralidoxime, obidoxime, HI-6) to reactivate Russian VX–inhibited acetylcholinesterase and to eliminate Russian VX–induced acute toxic effects was evaluated using in vivo methods. In vivo determined percentage of reactivation of Russian VX–inhibited blood and brain acetylcholinesterase in poisoned rats shows that HI-6 seems to be the most efficacious reactivator of Russian VX–inhibited acetylcholinesterase among currently used oximes in the peripheral compartment, whereas no difference between reactivating efficacy of all tested oximes was observed in the central compartment. The oxime HI-6 was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in Russian VX–poisoned mice among all studied oximes. Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings.

KA-672 inhibits rat brain acetylcholinesterase in vitro but not in vivo

1999 ◽  
Vol 263 (2-3) ◽  
pp. 193-196 ◽  
Author(s):  
Michael Hilgert ◽  
Michael Nöldner ◽  
Shyam S Chatterjee ◽  
Jochen Klein
Keyword(s):  
Rat Brain ◽  
Brain Acetylcholinesterase

Bispyridinium Oximes As Antidotal Treatment of Cyclosarin Poisoning—In Vitro and In Vivo Testing

2005 ◽  
Vol 24 (6) ◽  
pp. 399-402 ◽  
Author(s):  
Lucie Bartosova ◽  
Kamil Kuca ◽  
Daniel Jun ◽  
Gabriela Kunesova
Keyword(s):  
Rat Brain ◽  
Organophosphorus Compounds ◽  
Brain Homogenate ◽  
Chemical Structures ◽  
Hi 6 ◽  
In Vivo Testing ◽  
Acetylcholinesterase Enzyme ◽  
Enzyme Source

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents and less toxic pesticides, is based on the formation of irreversibly inhibited acetylcholinesterase, which causes cumulation of neuromediator acetylcholine in synaptic clefts and subsequent overstimulation of cholinergic receptors, that is followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic (atropine mostly) to counteract the accumulation of acetylcholine and acetylcholinesterase reactivators (pralidoxime or obidoxime) to reactivate inhibited acetylcholinesterase. In this study of cyclosarin poisoning treatment, oximes of different chemical structures (obidoxime, HI-6, BI-6, and HS-6) were tested in vitro on rat brain acetylcholinesterase (enzyme source: rat brain homogenate), and afterwards, they were tested in vivo in equimolar doses, in mice and rats. The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo.

scholarly journals Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

2008 ◽  
Vol 51 (4) ◽  
pp. 223-228 ◽  
Author(s):  
Jiří Bajgar
Keyword(s):  
Protective Effect ◽  
Cholinesterase Inhibitors ◽  
Acetylcholinesterase Inhibition ◽  
Prophylactic Effect ◽  
Hi 6 ◽  
Brain Acetylcholinesterase

The protective effect of the reversible cholinesterase inhibitors tacrine and pyridostigmine alone or in combination with different drugs against acetylcholinesterase inhibition in the pontomedullar area and cerebellum of rats caused by VX agent (O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate) in vivo (2xLD50) was studied along with survival of animals pretreated with different combinations of the drugs used. The best prophylactic effect was observed in a combination of pyridostigmine with benactyzine, trihexyphenidyle and HI-6. Tacrine alone or in other combinations has had no better prophylactic effect in comparison with these combinations containing pyridostigmine. Equine butyrylcholinesterase, also protected against VX poisoning very effectively.

scholarly journals A Comparison of the Potency of the Oxime HLö-7 and Currently Used Oximes (HI-6, Pralidoxime, Obidoxime) to Reactivate Nerve Agent-Inhibited Rat Brain Acetylcholinesterase by in vitro Methods

2005 ◽  
Vol 48 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Kamil Kuča ◽  
Jiří Cabal ◽  
Jiří Kassa ◽  
Daniel Jun ◽  
Martina Hrabinová
Keyword(s):  
Rat Brain ◽  
Nerve Agents ◽  
Nerve Agent ◽  
The Other ◽  
In Vitro Evaluation ◽  
In Vitro Methods ◽  
Hi 6 ◽  
Hlö 7 ◽  
Brain Acetylcholinesterase

1. The efficacy of the oxime HLö-7 and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate acetylcholinesterase inhibited by various nerve agents (sarin, tabun, cyclosarin, VX) was tested by in vitro methods. 2. Both H oximes (HLö-7, HI-6) were found to be more efficacious reactivators of sarin and VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase is very low and does not reach the reactivating efficacy of obidoxime. In the case of cyclosarin, the oxime HI-6 was only found to be able to sufficiently reactivate cyclosarin-inhibited acetylcholinesterase in vitro. 3. Thus, the oxime HLö-7 does not seem to be more efficacious reactivator of nerve agent-inhibited acetylcholinesterase than HI-6 according to in vitro evaluation of their reactivation potency and, therefore, it is not more suitable to be introduced for antidotal treatment of nerve agent-exposed people than HI-6.

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